The character of transition states and their interactions with enzymes will be determined for the series of enzymes that catalyze the transfer of intact methyl groups (methyl transferases). This information provides a logical basis for the rational design of agents which may inhibit, activate or otherwise affect the action of these enzymes. Such agents may be medically useful in conditions related to the action of these enzymes. The key technique is kinetic isotope effects applied to model reactions and to the enzyme reactions themselves, in combination with model vibrational analysis for interpretative purposes.